Biophysics Research and Lyme Disease

May is Lyme Disease Awareness Month in the US. Lyme disease is a bacterial infection primarily transmitted by Ixodes ticks (known as deer ticks) and black-legged ticks that can cause a wide variety of both temporary and chronic symptoms. The CDC estimates that 300,000 people are diagnosed with Lyme disease in the US every year, but Lyme disease is easily misdiagnosed, so the actual number with the disease could be significantly higher. We recently spoke with Biophysical Society member Charles Wolgemuth, University of Arizona, about his research on the bacterium that causes Lyme disease.

What is the connection between your research and Lyme disease?

Many cells are able to actively move themselves through their surroundings.  In order to do this, the cells must exert forces on their environment.  One of the main questions that my research asks is how do cells produce these forces and how do these forces drive the movements of the cells through various environments.  The bacterium that causes Lyme disease, Borrelia burgdorferi, is a fascinating organism.  It is very long (for a bacterium) and is quite thin (being only 300 nm in diameter).  It is also one of the most invasive mammalian pathogens, being able to invade many tissues in the mammal that other bacteria cannot access.  It “swims” through different tissues by undulating its entire body.  We are currently working to understand what about this bacterium’s motility makes it so adept at invading mammalian tissue, a critical aspect of the disease process in Lyme disease.

MATLAB Handle Graphics

This cartoon schematic shows the basic structure of these bacteria. The cell body is green and the helical filaments (flagella) are shown in purple. There are 7-11 flagella per cell end and they are anchored to tiny rotary motors. If you were to peel the flagella away from the cell body, the cell would straighten (as shown on the left side of the schematic).

Why is your research important to those concerned about Lyme disease?

Lyme disease occurs when a person is bitten by an Ixodes scapularis tick, a species of hard tick, infected with Borrelia burgdorferi.  These ticks feed for approximately 4-7 days.  The bacteria reside in the midgut of the tick.  During feeding, the bacteria start replicating and eventually (after about 40 hours) some of the bacteria break through the lining of the tick midgut and swim to the salivary glands.  The bacteria then break into the salivary glands and are deposited in the skin of the mammal through the tick saliva.  Once in the skin, the bacteria are able to move through the mammalian body, infecting many tissues such as the skin, joints, heart, and nervous system.  In order to do all this, these bacteria must be able to maneuver through a large range of different environments.  The symptoms of Lyme disease are caused by our bodies trying to fight off the bacterial infection.  It has been shown that the motility of B. burgdorferi is imperative for the bacterium to set up infection.  Therefore, understanding how this bacterium is so invasive and how its movement allows it to set up infection and evade our immune system is crucial for understanding this disease.

How did you get into this area of research?

Since graduate school, I have been fascinated by figuring out how different cells create the shapes of their bodies and how they move from place to place.  I got into working on Lyme disease when I heard about the shape of B. burgdorferi.  It is shaped like a wave! and achieves this by wrapping helical filaments around a cylindrical body.  The physics for how this works out was perplexing to me and captivated my interest.

How long have you been working on it?

I have been working on this for nearly 15 years.  I started thinking about the problem while I was a postdoc at UC Berkeley and then wrote a grant to work on the shape of B. burgdorferi during my first academic appointment at the University of Connecticut Health Center.

Do you receive public funding for this work? If so, from what agency?

We receive funding for this research from the National Institutes of Health.

Have you had any surprise findings thus far?

One of the first really exciting findings that we had was that we were able to show that the movements of these bacteria through gelatin (such as unsweetened Jello) is very similar to the movements through our skin.  Gelatin is basically a meshwork of protein, which is also true about the dermis of our skin.  Interestingly, the pores in the gelatin are substantially smaller than the diameter of these bacteria.  Therefore, B. burgdorferi has to push apart the gelatin in order to penetrate into it.  This finding has enabled us to develop an in vitro assay for studying how these bacteria invade into different tissues.  We have a couple really new results realted to invasion and the movement through gelatin that we are very excited about.  We haven’t published them yet, so I can’t say too much more than that at this time.

What is particularly interesting about the work from the perspective of other researchers?

I can’t speak for other researchers, but I think that one of the most interesting aspects of our work is that we have been able to link the physics of how these bacteria move to aspects of the disease process.  We recently developed a mathematical model for the early stages of Lyme disease that is based on the physics that we have determined from our gelatin assays.   We were able to show using this model why the rash that accompanies Lyme disease sometimes appear as a bull’s eye pattern.  The model also explains why these rashes grow so fast (around 1 cm in diameter per day).  The ability to go from the basic physics of the movement of these bacteria to an understanding of the disease itself I think is especially exciting.

What is particularly interesting about the work from the perspective of the public?

I would have to say the same thing that I just said:  We have shown that understanding the basic science of these organisms is informative about the disease process. Fifteen years ago when I started working on this, people would ask me what I was working on, and I would tell them that I was trying to figure out how the bacterium that causes Lyme disease creates its shape.  I would often get asked then about the practical application of figuring that out: how would understanding the shape of the bacterium help fight the disease?  How should I respond to this?  At that point of time, I didn’t know what we would figure out.  But it didn’t matter to me; it was an interesting question.  The way I see it, basic knowledge is worth an infinite amount more than any specific practical application.  Knowledge can be built upon and used in ways that no one can predict ahead of time.

With that, I will conclude with one thought for the general public: We must keep funding basic scientific questions, because we never know where a specific line of inquiry may lead us.  Science is not about foreseeable practical ends; it is about discovering things we never thought we would find.

 

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